The purpose of this study was to evaluate the clinical course and outcome for children with multicystic dysplastic kidney (MCDK) disease and to non-invasively predict which of these patients are at significant risk for developing urinary tract infection (UTI) and renal insufficiency. Patients were divided, on the basis of postnatal physical examination and renal ultrasonography, into simple or complex MCDK. Simple MCDK was defined as unilateral renal dysplasia without additional genitourinary (GU) abnormalities. Complex MCDK included patients with bilateral renal dysplasia or unilateral renal dysplasia with other GU abnormalities. The designation as simple or complex MCDK was independent of reflux, since routine voiding cystourethrography (VCUG) was not performed. The charts of all patients with the diagnosis of MCDK disease seen from August 1995 to March 1999 at Yale University School of Medicine were examined to determine: (1) if UTI had occurred and (2) the level of renal function at last follow-up. Thirty-five patients were evaluated: 28 (80%) patients had unilateral MCDK, 7 (20%) were bilateral, and 14 (40%) had associated GU anomalies. Overall, 21 patients had unilateral MCDK without GU abnormalities (simple MCDK), while 14 had complex MCDK. The final outcome for patients with simple MCDK was quite good, with normal renal function and compensatory hypertrophy of the contralateral kidney in all patients. Although the patients with simple MCDK did not have routine VCUG or prophylactic antibiotics, the development of UTI was infrequent, damage to the contralateral kidney did not occur, and renal function was well preserved. In contrast, patients with bilateral disease or associated GU anomalies had a higher incidence of UTI and progression to renal failure. Complex MCDK was associated with a worse outcome (50% chronic renal insufficiency or failure).